The role of endoplasmic reticulum in amyloid precursor protein processing and trafficking: implications for Alzheimer's disease

AI Plácido; CMF Pereira; AI Duarte; E Candeias; SC Correia; RX Santos; C Carvalho; S Cardoso; CR Oliveira; PI Moreira

doi:10.1016/j.bbadis.2014.05.003

The role of endoplasmic reticulum in amyloid precursor protein processing and trafficking: implications for Alzheimer's disease

AI Plácido, CMF Pereira, AI Duarte, E Candeias, SC Correia, RX Santos, C Carvalho, S Cardoso, CR Oliveira, PI Moreira^*

^*Corresponding author for this work

University of Coimbra

Research output: Contribution to journal › Article › peer-review

91 Citations (Scopus)

Abstract

The endoplasmic reticulum (ER) is the principal organelle responsible for the proper folding/processing of nascent proteins and perturbed ER function leads to a state known as ER stress. Mammalian cells try to overcome ER stress through a set of protein signaling pathways and transcription factors termed the unfolded protein response (UPR). However, under unresolvable ER stress conditions, the UPR is hyperactivated inducing cell dysfunction and death. The accumulation of misfolded proteins in the brain of Alzheimer's disease (AD) patients suggests that alterations in ER homeostasis might be implicated in the neurodegenerative events that characterize this disorder. This review discusses the involvement of ER stress in the pathogenesis of AD, focusing the processing and trafficking of the AD-related amyloid precursor protein (APP) during disease development. The potential role of ER as a therapeutic target in AD will also be debated.

Original language	English
Pages (from-to)	1444-1453
Number of pages	10
Journal	Biochimica et Biophysica Acta
Volume	1842
Issue number	9
Early online date	14 May 2014
DOIs	https://doi.org/10.1016/j.bbadis.2014.05.003
Publication status	Published - Sept 2014

Bibliographical note

Acknowledgments
Ana Plácido has a PhD fellowship from the Fundação para a Ciência e a Tecnologia (SFRH/BD/73388/2010).

The authors' work is supported by PEst-C/SAU/LA0001/2013-2014 and Gabinete de Apoio à Investigação (GAI)–Faculty of Medicine, University of Coimbra (MOREIRA05.01.13) and Banco Santader Totta.

Keywords

Alzheimer's disease
amyloid precursor protein
endoplasmic reticulum
secretory pathway
therapeutic targets
trafficking

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Plácido, AI., Pereira, CMF., Duarte, AI., Candeias, E., Correia, SC., Santos, RX., Carvalho, C., Cardoso, S., Oliveira, CR., & Moreira, PI. (2014). The role of endoplasmic reticulum in amyloid precursor protein processing and trafficking: implications for Alzheimer's disease. Biochimica et Biophysica Acta, 1842(9), 1444-1453. https://doi.org/10.1016/j.bbadis.2014.05.003

Plácido, AI, Pereira, CMF, Duarte, AI, Candeias, E, Correia, SC, Santos, RX, Carvalho, C, Cardoso, S, Oliveira, CR & Moreira, PI 2014, 'The role of endoplasmic reticulum in amyloid precursor protein processing and trafficking: implications for Alzheimer's disease', Biochimica et Biophysica Acta, vol. 1842, no. 9, pp. 1444-1453. https://doi.org/10.1016/j.bbadis.2014.05.003

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The role of endoplasmic reticulum in amyloid precursor protein processing and trafficking: implications for Alzheimer's disease

Abstract

Bibliographical note

Keywords

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